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1.
Sensors (Basel) ; 24(9)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38733005

RESUMO

With the rapidly growing interest in using structural timber, a need exists to inspect and assess these structures using non-destructive testing (NDT). This review article summarizes NDT methods for wood inspection. After an overview of the most important NDT methods currently used, a detailed review of Ground Penetrating Radar (GPR) and Ultrasonic Testing (UST) is presented. These two techniques can be applied in situ and produce useful visual representations for quantitative assessments and damage detection. With its commercial availability and portability, GPR can help rapidly identify critical features such as moisture, voids, and metal connectors in wood structures. UST, which effectively detects deep cracks, delaminations, and variations in ultrasonic wave velocity related to moisture content, complements GPR's capabilities. The non-destructive nature of both techniques preserves the structural integrity of timber, enabling thorough assessments without compromising integrity and durability. Techniques such as the Synthetic Aperture Focusing Technique (SAFT) and Total Focusing Method (TFM) allow for reconstructing images that an inspector can readily interpret for quantitative assessment. The development of new sensors, instruments, and analysis techniques has continued to improve the application of GPR and UST on wood. However, due to the hon-homogeneous anisotropic properties of this complex material, challenges remain to quantify defects and characterize inclusions reliably and accurately. By integrating advanced imaging algorithms that consider the material's complex properties, combining measurements with simulations, and employing machine learning techniques, the implementation and application of GPR and UST imaging and damage detection for wood structures can be further advanced.

2.
Blood ; 137(5): 600-609, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538797

RESUMO

The phase 2 CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC+). Eligible patients were ≥18 years of age and had previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2 to 5. Venetoclax 800 mg (days 4-10, cycle 1; days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and cyclophosphamide, doxorubicin, vincristine, and prednisone (6-8 cycles) in 21-day cycles. Primary end points were safety, tolerability, and research_plete response (CR) at end of treatment (EOT). Secondary end points were progression-free survival (PFS) and overall survival. Comparative analyses used covariate-adjusted R-CHOP controls from the GOYA/BO21005 study, an appropriate contemporary benchmark for safety and efficacy. Safety and efficacy analyses included 206 patients. CR rate at EOT was 69% in the overall population and was maintained across Bcl-2 IHC+ subgroups. With a median follow-up of 32.2 months, trends were observed for improved investigator-assessed PFS for venetoclax plus R-CHOP in the overall population (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.43-0.87) and Bcl-2 IHC+ subgroups (HR, 0.55; 95% CI, 0.34-0.89) vs R-CHOP. Despite a higher incidence of grade 3/4 hematologic adverse events (86%), related mortality was not increased (2%). Chemotherapy dose intensity was similar in CAVALLI vs GOYA. The addition of venetoclax to R-CHOP in 1L DLBCL demonstrates increased, but manageable, myelosuppression and the potential of improved efficacy, particularly in high-risk Bcl-2 IHC+ patient subgroups.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Fadiga/induzido quimicamente , Feminino , Gastroenteropatias/induzido quimicamente , Genes bcl-2 , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Doenças Hematológicas/induzido quimicamente , Humanos , Infecções/etiologia , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/antagonistas & inibidores , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
3.
Blood ; 136(23): 2628-2637, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-32785666

RESUMO

This open-label phase 2 study (CONTRALTO) assessed the safety and efficacy of BCL-2 inhibitor venetoclax (VEN) plus rituximab (R), and VEN plus bendamustine (B) and R, vs B + R (BR) alone in relapsed/refractory (R/R) follicular lymphoma. Patients in the chemotherapy-free arm (arm A: VEN + R) received VEN 800 mg/d plus R 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 4, 6, 8, 10, and 12. After a safety run-in with VEN 600 mg, patients in the chemotherapy-containing cohort were randomized to either VEN + BR (arm B; VEN 800 mg/d for 1 year + 6 cycles of BR [B 90 mg/m2 on days 1 and 2 and R 375 mg/m2 on day 1]) or 6 cycles of BR (arm C). Overall, 163 patients were analyzed (9 in the safety run-in and 52, 51, and 51 in arms A, B, and C, respectively). Complete metabolic/complete response rates were 17% (arm A), 75% (arm B), and 69% (arm C). Of patients in arm B, only 61% received ≥90% of the planned B dose vs 96% of patients in arm C. More frequent hematologic toxicity resulted in more reduced dosing/treatment discontinuation in arm B vs arm C. Rates of grade 3/4 adverse events were 51.9%, 93.9%, and 60.0% in arms A, B, and C, respectively. VEN + BR led to increased toxicity and lower dose intensity of BR than in arm C, but efficacy was similar. Optimizing dose and schedule to maintain BR dose intensity may improve efficacy and tolerability of VEN + BR, while VEN + R data warrant further study. This study was registered at www.clinicaltrials.gov as #NCT02187861.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos
4.
J Assoc Physicians India ; 70(9): 11-12, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36082891

RESUMO

Burkitt's lymphoma (BL), a variety of non-Hodgkin's lymphoma, is uncommon in India. Cardiac involvement in sporadic BL is rare. Cardiac involvement may be primary or a part of a systemic disease process. It affects the endocardium, myocardium, or pericardium. Cardiac symptoms may or may not be present in the early clinical stages. We are presenting a case of sporadic BL in a 13-year-old child with cardiac and systemic involvement.


Assuntos
Linfoma de Burkitt , Adolescente , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/patologia , Humanos , Índia
5.
Blood ; 133(18): 1964-1976, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30850381

RESUMO

Novel strategies, such as chemosensitization with targeted agents, that build on the success of standard immunochemotherapy show promise for the treatment of non-Hodgkin lymphoma (NHL). Here, we report a phase 1b study investigating dose escalation of the BCL2 inhibitor, venetoclax, in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP) chemotherapy in B-cell NHL. Objectives included safety assessment and determination of a recommended phase 2 dose (RP2D). Fifty-six patients were enrolled, most with follicular lymphoma (43%) or diffuse large B-cell lymphoma (DLBCL; 32%). Dose-limiting toxicities were reported in 3/14 patients at the first venetoclax dose (200 mg/d), after which dosing was changed from daily to 10 days per cycle and escalated to 800 mg. A further reduction to 5 days per cycle occurred at the 800-mg dose level in the G-CHOP arm. Cytopenias were predominant among grade 3/4 events and reported at a higher rate than expected, particularly in the G-CHOP arm; however, safety was manageable. Overall response rates were 87.5% (R-CHOP and G-CHOP combinations); complete response (CR) rates were 79.2% and 78.1%, respectively. Most double-expressor (BCL2+ and MYC+) DLBCL patients (87.5%; n = 7/8) achieved CR. Although the maximum tolerated dose was not reached, the RP2D for venetoclax with R-CHOP was established at 800 mg days 4 to 10 of cycle 1 and days 1 to 10 of cycles 2 to 8; higher doses were not explored, and this dosing schedule demonstrated an acceptable safety profile. This regimen is subsequently being evaluated in first-line DLBCL in the phase 2 portion of the study. This trial was registered at www.clinicaltrials.gov as #NCT02055820.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Vincristina/uso terapêutico
6.
Lancet Oncol ; 21(9): 1188-1200, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888452

RESUMO

BACKGROUND: Venetoclax plus obinutuzumab has been established as a fixed-duration treatment regimen for patients with chronic lymphocytic leukaemia. We compared the long-term efficacy after treatment cessation of the combination of venetoclax plus obinutuzumab with chlorambucil plus obinutuzumab in patients with previously untreated chronic lymphocytic leukaemia. METHODS: CLL14 is a multicentre, randomised, open-label, phase 3 trial done at 196 sites in 21 countries. Eligible patients were aged 18 years or older, had untreated chronic lymphocytic leukaemia, and coexisting conditions with a cumulative illness rating scale greater than 6, a creatinine clearance of 30-69 mL/min, or both. Patients were randomly assigned (1:1) via a web and voicemail system with allocation concealment and based on a computer-generated randomisation schedule with a block size of six and stratified by Binet stage and geographical region. Patients received either venetoclax plus obinutuzumab (oral venetoclax initiated on day 22 of cycle 1 [28-day cycles], with a 5-week dose ramp-up [20 mg, 50 mg, 100 mg, and 200 mg, then 400 mg daily for 1 week], thereafter continuing at 400 mg daily until completion of cycle 12; combined with intravenous obinutuzumab for six cycles starting with 100 mg on day 1 and 900 mg on day 2 [or 1000 mg on day 1], 1000 mg on days 8 and day 15 of cycle 1, and subsequently 1000 mg on day 1 of cycles 2 through 6) or chlorambucil plus obinutuzumab (oral chlorambucil at 0·5 mg/kg bodyweight on days 1 and 15 of each cycle for 12 cycles combined with the same obinutuzumab regimen). The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. Patient enrolment is complete, and the study is registered with ClinicalTrails.gov, NCT02242942. FINDINGS: Between Aug 7, 2015, and Aug 4, 2016, 432 patients were enrolled and randomly assigned to receive either venetoclax plus obinutuzumab (n=216) or chlorambucil plus obinutuzumab (n=216). All patients had been off treatment for at least 24 months at data collection. At a median follow-up of 39·6 months (IQR 36·8-43·0), patients given venetoclax plus obinutuzumab had a significantly longer progression-free survival than did patients given chlorambucil plus obinutuzumab (HR 0·31, 95% CI 0·22-0·44; p<0·0001). Median progression-free survival was not reached (95% CI not estimable to not estimable) in the venetoclax plus obinutuzumab group vs 35·6 months (33·7-40·7) in the chlorambucil plus obinutuzumab group. The most common grade 3 or 4 adverse event in both groups was neutropenia (112 [53%] of 212 patients in the venetoclax plus obinutuzumab group versus 102 [48%] of 214 patients in the chlorambucil plus obinutuzumab group). Serious adverse events occurred in 115 (54%) of 212 patients in the venetoclax plus obinutuzumab group and 95 (44%) of 214 patients in the chlorambucil plus obinutuzumab group. Venetoclax or chlorambucil treatment-related deaths were reported in one (1%) of 212 patients in the venetoclax plus obinutuzumab group (n=1 sepsis) and two (1%) of 214 patients in the chlorambucil plus obinutuzumab group (n=1 septic shock, n=1 metastatic skin squamous carcinoma). INTERPRETATION: 2 years after treatment cessation, venetoclax plus obinutuzumab continues to significantly improve progression-survival compared with chlorambucil plus obinutuzumab, thereby providing a limited duration treatment option for patients with previously untreated chronic lymphocytic leukaemia. FUNDING: F Hoffmann-La Roche and AbbVie.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Clorambucila/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Sulfonamidas/administração & dosagem , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Clorambucila/efeitos adversos , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Sulfonamidas/efeitos adversos , Resultado do Tratamento
7.
Stat Sin ; 25(4): 1613-1635, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26576105

RESUMO

Survival data often contain tied event times. Inference without careful treatment of the ties can lead to biased estimates. This paper develops the Bayesian analysis of a stochastic wear process model to fit survival data that might have a large number of ties. Under a general wear process model, we derive the likelihood of parameters. When the wear process is a Gamma process, the likelihood has a semi-closed form that allows posterior sampling to be carried out for the parameters, hence achieving model selection using Bayesian deviance information criterion. An innovative simulation algorithm via direct forward sampling and Gibbs sampling is developed to sample event times that may have ties in the presence of arbitrary covariates; this provides a tool to assess the precision of inference. An extensive simulation study is reported and a data set is used to further illustrate the proposed methodology.

8.
Adm Policy Ment Health ; 42(2): 176-85, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24879633

RESUMO

The objective of this study is to test the hypotheses that bipolar disorders or depressive disorders, minority status, and the presence of pediatric inpatient psychiatric unit will be individual predictors of pediatric psychiatric inpatient admission, and to provide a model that will evaluate which individual and organizational characteristics predict pediatric psychiatric inpatient. For this purpose, a secondary analysis of the medical records of 1,520 pediatric patient visits between January 1, 2008 and June 30, 2008, was conducted using univariate and multivariate logistic regression. Independent predictors of pediatric psychiatric inpatient admission were presence of bipolar and depressive disorders, greater average daily census, and increasing operating margin. Minority status was a significant predictor of not being admitted, as was presence of an anxiety disorder, greater total margin and older age. The results indicate that both individual and organizational factors impact disposition outcomes in particular subsets of pediatric patients who present to emergency departments for psychiatric reasons.


Assuntos
Etnicidade/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Grupos Minoritários/estatística & dados numéricos , Transtornos de Adaptação/epidemiologia , Adolescente , Transtornos de Ansiedade/epidemiologia , Transtorno Bipolar/epidemiologia , Criança , Pré-Escolar , Transtorno da Conduta/epidemiologia , Connecticut/epidemiologia , Transtorno Depressivo/epidemiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Pediatria , Unidade Hospitalar de Psiquiatria , Fatores de Risco
9.
Data Brief ; 55: 110698, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39044908

RESUMO

Biological durability remains an understudied area of mass timber construction, despite expert warnings on potential moisture and decay issues that may affect building performance. In an effort to bridge the knowledge gap, this article presents experimental data on the performance of fungal-decayed cross laminated timber (CLT) connection assemblies. A total of 560 connection assemblies were made using select CLT species from major global markets. These were mechanically tested following inoculation by two brown rot fungi for a total period of 78 weeks, with the connections periodically harvested after 10, 20, 30, 40, 52, and 78 weeks. The data from the mechanical tests, which included cyclic evaluation using an abbreviated CUREE loading protocol and dowel bearing strength tests performed in accordance with ASTM D5764, are submitted in this repository. The repository also contains information on mass changes to connection assemblies as decay progressed and SAWS model parameters that were calibrated using the raw data generated from the universal testing machine (UTM) during cyclic tests of the connection assemblies. This work is fundamental for accurate assessment of fungal deterioration in mass timber buildings and the data submitted herein could be used by researchers and scientists to model behavior of connections in mass timber buildings, especially in humid and damp regions with high chances of biodeterioration.

10.
Nanoscale ; 15(34): 14081-14092, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37581308

RESUMO

Advancements in photovoltaic research suggest that tin-based perovskites are potential alternatives to traditional lead-based structures. Cs2SnI6, specifically, stands out as a notable candidate, exhibiting impressive performance. However, its complete potential remains untapped primarily owing to the limited understanding of its photophysics. In light of this, this study aims to bridge this knowledge gap. To commence our study, we first executed theoretical investigations to locate the energetically diverse excitons within the Brillouin zone. Building on this knowledge, we then utilized transient absorption spectroscopy to investigate their temporal evolution. Herein, we observed the formation of high-energy excitons even when the incident photon energy was below the necessary threshold, which is quite distinctive and intriguing. Of particular interest is the generation of ultraviolet (UV) domain exciton using visible photons, which implies that Cs2SnI6 has the potential for efficient solar light harvesting. Tracking the kinetics revealed that this unique finding arises due to the intertwined formation and decay pathways undertaken by the different excitons, aided by intervalley scattering and phonon absorption processes. In addition, we found that the decay of the UV exciton was unusually slow. Transient mobility investigations were undertaken to probe the carrier transport behavior that further established hot carriers (HCs) in Cs2SnI6 to be highly mobile and susceptible to polaron formation. Overall, our findings demonstrate that Cs2SnI6 is a strong candidate for HC-based photovoltaics because it possesses all the prerequisites desired for such applications.

11.
Sci Total Environ ; 864: 161067, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36565890

RESUMO

The uncertainties of the environment and the emission levels of nonrenewable resources have compelled humanity to develop sustainable energy savers and sustainable materials. One of the most abundant and versatile bio-based structural materials is wood. Wood has several promising advantages, including high toughness, low thermal conductivity, low density, high Young's modulus, biodegradability, and non-toxicity. Furthermore, while wood has many ecological and structural advantages, it does not meet optical transparency requirements. Transparent wood is ideal for use in various industries, including electronics, packaging, automotive, and construction, due to its high transparency, haze, and environmental friendliness. As a necessary consequence, current research on developing fine wood is summarized in this review. This review begins with an explanation of the history of fine wood. The concept and various synthesis strategies, such as delignification, refractive index measurement methods, and transparent lumber polymerization, are discussed. Approaches and techniques for the characterization of transparent wood are outlined, including microscopic, Fourier transform infrared (FTIR), and X-ray diffraction (XRD) analysis. Furthermore, the characterization, physical properties, mechanical properties, optical properties, and thermal conductivity of transparent wood are emphasized. Eventually, a brief overview of the various applications of fine wood is presented. The present review summarized the first necessary actions toward future transparent wood applications.

12.
Adv Ther ; 39(1): 598-618, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34822104

RESUMO

INTRODUCTION: Outcomes remain poor in patients with diffuse large B cell lymphoma (DLBCL) who overexpress BCL-2 protein. We present population pharmacokinetics (PopPK) and exposure-response (ER) analyses for venetoclax (a selective BCL-2 inhibitor) administered with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with relapsed/refractory (R/R) and previously untreated (1L) non-Hodgkin lymphoma (NHL) from the phase 1b/2 CAVALLI study, to confirm dose selection for future studies. METHODS: Analyses included 216 patients with R/R or 1L NHL treated for eight 21-day cycles with 400-800 mg venetoclax (cycle 1: days 4-10; cycles 2-8: days 1-10) in combination with R for eight cycles and CHOP for 6-8 cycles. A legacy PopPK model for venetoclax was used to describe the observed data and provide post hoc PK parameters. Venetoclax steady-state exposure (AUCss) was used to predict clinical efficacy, safety, or tolerability. To isolate the effect of venetoclax, ER analyses referenced data from the R-CHOP arm of a historical control study, GOYA, in 1L DLBCL. RESULTS: There was no significant association between venetoclax AUCss and progression-free survival or complete response either for all-comers or the BCL-2-immunohistochemistry-positive subpopulation. No statistically significant trends were observed with venetoclax AUCss and the key grade ≥ 3 adverse events and serious adverse events. Similar dose intensities were observed for venetoclax and R-CHOP components across venetoclax exposures, suggesting venetoclax did not impact delivery of the R-CHOP backbone. CONCLUSIONS: The PopPK and ER analyses, in addition to the positive benefit-risk observed in the clinical data, support the selection of 800 mg venetoclax given with R-CHOP for future studies in BCL-2-immunohistochemistry-positive patients with 1L DLBCL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02055820.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linfoma Difuso de Grandes Células B , Sulfonamidas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
13.
Adv Ther ; 39(8): 3635-3653, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35708885

RESUMO

INTRODUCTION: This study aims to investigate pharmacokinetics (PK) and exposure-response parameters of the 400 mg once-daily venetoclax dose regimen in combination with obinutuzumab, which was approved for the first-line (1L) treatment of chronic lymphocytic leukemia (CLL) based on data from the phase 3 CLL14 study and the phase 1b dose-finding GP28331 study. METHODS: Parameter estimates and uncertainty, which were estimated by a previously developed population PK (popPK) model, were used as informative priors for this analysis. They were re-estimated, and then used to evaluate additional covariate effects, describe venetoclax PK when administered with obinutuzumab, and provide empirical Bayes estimates of PK parameters and exposure. Exposure-progression-free survival (PFS) and exposure-safety relationships were assessed using data from CLL14, with steady-state nominal venetoclax exposure (CmeanSS,nominal) as the predictor variable. Exposure-safety analyses were conducted using logistic regression for selected treatment-emergent grade ≥ 3 adverse events (AEs) and serious AEs (SAEs). Dose intensities were summarized by tertiles of CmeanSS,nominal. RESULTS: PK data from 274 patients (CLL14, n = 194; GP28331, n = 80) were included. The final model provided good fit of the observed data. Obinutuzumab co-administration, history of prior treatments, and disease severity at baseline had no appreciable influence on venetoclax steady-state exposure. No significant correlations were observed between venetoclax exposure and PFS, or between venetoclax exposure and the probability of treatment-emergent grade ≥ 3 neutropenia, grade ≥ 3 thrombocytopenia, grade ≥ 3 infections, and SAEs. Median dose intensities for venetoclax and obinutuzumab remained similar across venetoclax exposure tertiles. CONCLUSION: PopPK and exposure-efficacy, exposure-safety, and exposure-tolerability analyses support the 400 mg once-daily venetoclax dose plus obinutuzumab for 1L treatment in patients with CLL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifiers NCT02242942 and NCT02339181.


Assuntos
Leucemia Linfocítica Crônica de Células B , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Teorema de Bayes , Compostos Bicíclicos Heterocíclicos com Pontes , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Sulfonamidas
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 250: 119368, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33406451

RESUMO

Sb2S3 hollow-spheres in powder form were synthesized through a facile chemical route. The synthesized material was found to have notably high specific surface area. After annealing it showed broadband absorption of light within the visible region. The valance band and conduction band of the synthesized semiconductor were also positioned appropriately (w.r.t NHE) so that the required redox reactions with water in presence of the photogenerated excitons are facilitated. These factors make it a suitable candidate for photocatalytic applications towards the degradation of dye based water pollutants. The synthesized material was established through systematic structural, compositional and optical characterizations. The photocatalytic efficacy toward the degradation of cationic, anionic and neutral dyes has been studied and the best degradation efficiency of 99.72% within 20 min has been achieved at a rate of 0.2920/min, which is significantly higher than many previous reports. Reusability, one of the major factors for the practical application of a catalyst, has also been studied in detail by investigating the probable changes in structural properties as well as in performance after several cycles of photodegradation. The reliability studies yielded encouraging results even after 50th cycle of photodegradation. The effect of catalyst loading on the photodegradation efficacy has also been studied.

15.
Macromol Biosci ; 21(1): e2000179, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017096

RESUMO

In this review, few established cell printing techniques along with their parameters that affect the cell viability during bioprinting are considered. 3D bioprinting is developed on the principle of additive manufacturing using biomaterial inks and bioinks. Different bioprinting methods impose few challenges on cell printing such as shear stress, mechanical impact, heat, laser radiation, etc., which eventually lead to cell death. These factors also cause alteration of cells phenotype, recoverable or irrecoverable damages to the cells. Such challenges are not addressed in detail in the literature and scientific reports. Hence, this review presents a detailed discussion of several cellular bioprinting methods and their process-related impacts on cell viability, followed by probable mitigation techniques. Most of the printable bioinks encompass cells within hydrogel as scaffold material to avoid the direct exposure of the harsh printing environment on cells. However, the advantages of printing with scaffold-free cellular aggregates over cell-laden hydrogels have emerged very recently. Henceforth, optimal and favorable crosslinking mechanisms providing structural rigidity to the cell-laden printed constructs with ideal cell differentiation and proliferation, are discussed for improved understanding of cell printing methods for the future of organ printing and transplantation.


Assuntos
Materiais Biocompatíveis/química , Bioimpressão , Impressão Tridimensional , Engenharia Tecidual , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Humanos , Hidrogéis/química , Tinta , Reologia , Estresse Mecânico , Alicerces Teciduais
16.
J Mech Behav Biomed Mater ; 102: 103494, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31654991

RESUMO

Strontium (Sr), a mineral element present in trace in the human body, has significant effect on bone remodelling. Sr containing ceramics have huge potential to heal bone defects and improve osseointegration of implants. In this study, perovskite oxide - strontium titanate (SrTiO3) was synthesized and explored its potential for biomedical applications. The phase pure SrTiO3 powder was synthesized from solid state reaction of strontium carbonate (SrCO3) and titanium dioxide (TiO2) at 1200 °C for 2 h. The as synthesized SrTiO3 powder, pure hydroxyapatite (HAp) and SrTiO3-50 wt% HAp (SH50) premixed powders were sintered at different temperatures varies from 1100 to 1400 °C in air. The sintered samples were characterized using X-ray diffraction (XRD) for phases and scanning electron microscopy (SEM) for microstructure analysis. XRD results revealed no dissociation of HAp or reaction with SrTiO3 during sintering. The sintered samples were studied for mechanical properties, wettability, and biocompatibility. The relative density of the sintered SrTiO3 increases with increasing sintering temperature. The relative density of SrTiO3 was increased from 77% to 98% with increase in sintering temperature from 1250 to 1400 °C. The substantial improvement of hardness and compressive strength was observed for sintered SrTiO3 compared to HAp of similar porosity level. The hardness and compressive strength of SrTiO3 sintered at 1250 °C found ~6 and ~3.5 times higher than sintered HAp. In vitro dissolution study carried out in phosphate buffer solution at 37 °C, confirmed the release of Sr2+ ion from the bulk SrTiO3 sintered at 1250 °C. The in vitro cell materials interaction showed cytocompatibility of sintered SrTiO3 and SrTiO3-HAp composite. In summary, excellent biocompatibility of SrTiO3 with superior mechanical properties confirmed its potential as novel biomaterial for use in the repair of infected or aseptic bone defects.


Assuntos
Materiais Biocompatíveis , Estrôncio , Cerâmica , Humanos , Óxidos , Titânio
17.
Indian J Endocrinol Metab ; 24(6): 532-536, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33643870

RESUMO

CONTEXT: There is scarcity of data on thyroid function abnormality in COVID-19 patients in world literature. AIMS: The objective of this study was to assess thyroid function tests in hospitalized patients of COVID-19. SETTINGS AND DESIGN: Sixty (60) patients with COVID-19 detected by RT-PCR admitted in General Medicine isolation ward and COVID block of a tertiary care teaching hospital were selected by semi-purposive sampling. MATERIALS AND METHODS: These patients were assessed for thyroid function tests, including total T3, free T3, total T4, free T4, TSH and anti-TPO antibody along with other baseline investigations. Patients with pre-existing thyroid-related ailments, those on levothyroxine or anti-thyroid drugs or other drugs known to interfere with the results were excluded. RESULTS: There were 43.3% patients in mild, 26.7% in moderate, and 30% in severe category, according to local COVID-19 severity classification protocol. 35% patients had one or more abnormality in the thyroid function, low TSH being the most common (18.33%). 9.1% patients had characteristic pattern of thyroiditis. In most of the others thyroid function did not match any typical pattern. There was no significant difference in any of the parameters of the thyroid function test between mild, moderate, and severe groups. CONCLUSION: Thyroid function may be abnormal in all categories of patients during COVID-19 infection, even in absence of pre-existing thyroid ailments. Although low TSH is the commonest abnormality and typical pattern of thyroiditis can be seen in a subsection of patients, in majority of the patients, thyroid function abnormality does not follow any characteristic pattern and likely represents a combination of thyroiditis and sick euthyroid syndrome in different points of its spectrum.

19.
J Mech Behav Biomed Mater ; 95: 136-142, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30995580

RESUMO

Fluorine substituted hydroxyapatite (FAp) with different degree of fluorine (F) substitution, has been synthesized using hydrothermal synthesis method. In the present work, as synthesized powders were consolidated by sintering at 1200 °C in air for 1 h. The sintered specimens were characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) for phase analysis. Further, fluorine intake in the sintered specimens was evaluated using ion chromatography (IC). XRD peaks clearly showed biphasic nature of the sintered specimen. However, the sintered samples containing more than ∼60% fluorine substitution showed no ß-tricalcium phosphate (ß-TCP) phase formation. The IC results revealed that the degree of fluoridation decreased significantly in the sintered specimen compare to the respective as synthesized powders. The effect of actual fluorine content in the sintered specimens was further evaluated in terms of sinterability, surface energy, mechanical properties and in vitro cytocompatibility study. The surface energy of the sintered specimen decreased from 51.8 mN/m to 42.5 mN/m, in which degree of fluoridation varies from 0% to 110%. The in vitro cytocompatibility of the sintered specimen were carried out against mouse osteoblast cell line (MC3T3-E1). In vitro study showed that all the samples were nontoxic but cell proliferation for the samples containing more than 40% fluorine substitution became significantly low.


Assuntos
Durapatita/química , Durapatita/farmacologia , Flúor/química , Células 3T3 , Animais , Teste de Materiais , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Relação Estrutura-Atividade , Propriedades de Superfície
20.
J Mech Behav Biomed Mater ; 90: 328-336, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30399562

RESUMO

Synthesis of strontium-doped hydroxyapatite from Mercenaria clam shells has been carried out by hydrothermal method. The doping of bioceramic, processed from biogenic resources is mostly unexplored. The objective is to understand the effect of strontium (Sr) incorporation on phase stability, sintering behaviour, mechanical properties and cytotoxicity of hydroxyapatite (HAp) derived from clam shells. The different molar concentrations of Sr, varies from 10, 30, 50, 70% of Ca, were substituted into the HAp. The synthesized powders were sintered at 1200 °C in air. The as synthesized powders and sintered specimens were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and high resolution transmission electron microscopy. The crystallite size and cell parameters of sintered specimens were analyzed from XRD. The XRD of hydrothermally synthesized powders mostly matched with HAp with slight shifting due to Sr doping. However, some distinct Sr based compounds were also observed where Sr substitution is more that 50% of Ca. The XRD of sintered specimen showed increasing ß-tricalcium phosphate (ß-TCP) phase with Sr substitution. The sintered density of solid samples gradually increased from 3.04 g/cc to 3.50 g/cc and surface energy decreased with increasing Sr substitution. Similarly, microhardness, fracture toughness and nanohardness of solid samples found to be enhanced with Sr substitution. The elastic modulus gradually increased from 130 to 137 GPa for HAp and Sr substituted HAp (70% of Ca). The in vitro cytotoxicity of sintered specimen against mouse osteoblast cell line showed that all the samples were nontoxic. However cell proliferation found low for the solid samples containing more than 50% Sr substitution.


Assuntos
Exoesqueleto/química , Durapatita/química , Durapatita/síntese química , Fenômenos Mecânicos , Mercenaria/anatomia & histologia , Estrôncio/química , Células 3T3 , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Técnicas de Química Sintética , Durapatita/toxicidade , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Transição de Fase , Propriedades de Superfície
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